Past research has focussed on achieving a more precise characterization of the dementia syndrome in HD and relating it to other clinical and neuroradiological features. In the next funding period, three studies are planned: 1) A 5-year, longitudinal study of dementia in HD will be performed. Forty new patients per year will be entered and will have annual neuropsychological examinations and biannual brain MRI scans. Alterations in particular cognitive domains over time will be assessed as a function of age of onset of disease and asymmetries in clinical presentation. Patterns of impairment and rate of change will be related to measures of frontal cortical and striatal degeneration on MRI scans. 2) Memory deficits will be subject to further study, concentrating on aspects of explicit memory (recall and recognition) and implicit memory (skill acquisition, priming, and activation). It is proposed that performance on experimental task of explicit memory will be correlated to MRI measures of frontal cortical atrophy, while implicit memory task performance will be related to striatal degeneration. 3) The factors that render HD patients disabled will be assessed. The relative contributions of poor motor control, specific cognitive deficits, and emotional symptoms and disorders will be evaluated. Sources of occupational disability will be sought in patients' longitudinal neuropsychological performance and by interviews with employers. Impaired ability to drive an automobile will be assessed in a driving simulator and the results correlated with neuropsychological test performance. These studies will further our understanding of the relationship between fronto-striatal pathology and specific cognitive impairments in HD, while at the same time provide practical knowledge that will be valuable in the care and management of afflicted patients.